Human Reproduction Unit

The Human Reproduction Unit aims to investigate the causes and effective treatment for infertility, including diseases of reproductive health like endometriosis and the decline in fertility with age. We also investigate the effects of poor health in parents during pregnancy on the health of their babies throughout life.

The unit is a pioneer in the development of modern forms of assisted reproductive medicine. It produced the first IVF babies in Sydney and pioneered the development of ICSI, pre-implantation embryo biopsy and genetic diagnosis. Our unit has played a key role in the development of improved embryo culture procedures. Yet, despite 40 years of progress with assisted reproduction procedures, there is still a long way to go, with more than 80 per cent of embryos failing to result in viable offspring. Our team strives to understand and find ways of overcoming these challenges.


Lead

Christopher O’Neill, PhD

Professor of Reproductive and Developmental Medicine
Departments of Medicine (Northern Clinical School) and Physiology (School of Medical Science)

Yan Li, PhD


Senior Research Fellow

Greg Mulhearn, B. Eng.


Scientific Officer

  • Charles Perkins Centre
  • NSW Reproduction Forum
  • North Shore Multi-disciplinary Endometriosis 
  • Research and Clinical Care Consortium

Why are the rates of childhood cancer increasing?

Parents are attempting to achieve pregnancy later in their lives and are more likely to have chronic diseases, such as obesity, diabetes or cardiovascular disease at the time of conception. These states impose a range of cellular stresses on the gametes and early embryo, reducing the embryo's chance of surviving to birth. The embryos that do survive these stresses have a range of genetic and epigenetic characteristics that favour their survival. These characteristics are also the same cellular traits that favour the conversion of normal cells into cancer cells. This study investigates how the range of stresses to the gametes and early embryo created by modern lifestyles interact with the genetic and epigenetic landscape of the embryo to influence their survival. We investigate how the characteristics of the embryos that survive may predispose the resulting offspring to the onset of chronic non-communicable diseases, including cancer. A detailed molecular understanding of the processes involved will guide changes in policy and practice to minimise and treat the risks.

The causes and treatments of the loss of fertility with maternal age

Societal changes mean there is a major shift with couples starting their family much later in life. For both men and women, fertility decreases with age and this is particularly severe in women after the age of around 35. There are many reasons for this decline including the formation of eggs with very serious genetic abnormalities. These abnormalities are commonly of such severity that they prevent the normal formation of the early embryo. Our unit investigates the molecular basis for this rise in genetic errors. Recent progress in this area points to potential new strategies for alleviating this condition and a detailed molecular understanding of the processes will help define future therapeutic directions.

Understanding the causes of endometriosis

Endometriosis is a disease that affects approximately 10 per cent of women and girls. It causes debilitating chronic abdominal pain and is a common cause of infertility. There are currently limited treatment options and it remains a major disease burden within the community. Endometriosis results from the growth of the cells that normally line the uterus in other abdominal organs. The body has a range of normal processes that prevents such ectopic growth, but these are circumvented in endometriosis. This project examines the processes of cell and genetic regulation of endometriotic tissue growth that allows it to escape the normal surveillance mechanisms that prevent ectopic growth. A detailed understanding of the biology of this disease will point to new therapeutic strategies.  

Bertoldo MJ et al. (2019) NAD+ repletion rescues female fertility during reproductive ageing. bioRχiv. doi: https://doi.org/10.1101/721985

Hills, R., et al. (2019). "Platelet-activating factor receptor (version 2019.4) in IUPHAR/BPS Guide to Pharmacology Database " IUPHAR/BPS Guide to Pharmacology CITE, 2019(4)
2019(4).

O’Neill, C. (2017) Dynamic Changes in DNA Modifications During Key Embryonic Transitions. In Handbook of Epigenetics, 2nd Edition (ed T Tollefsbol) London, 261-76.

Li Y, O’Neill C (2017) Immunological Staining of Global Changes in DNA Methylation in the Early Mammalian Embryo. Methods in Molecular Biology. Zygotic Genome Activation: Methods and Protocols. K. Lee. New York, NY, Springer New York: 161-169

Rollo, C., et al. (2017). "Histone 3 lysine 9 acetylation is a biomarker of the effects of culture on zygotes." Reproduction 154: 375-385

Ganeshan, L., et al. (2017). "The induction of tumour suppressor protein P53 limits the entry of cells into the pluripotent inner cell mass lineage in the mouse embryo." Experimental Cell Research 358(2): 227-233.

Li Y, Seah MK,O'Neill C. 2016 Mapping global changes in nuclear cytosine base modifications in the early mouse embryo. Reproduction. Feb;151(2):83-95. doi: 10.1530/REP-15-0207.

Çelik S, Li Y, O'Neill C. (2015) The effect of DNA damage on the pattern of immune-detectable DNA methylation in mouse embryonic fibroblasts. Exp Cell Res. Nov 15;339(1):20-34.

Salvaing, J. et al (2015). Determinants of valid measurement of global changes in 5′-methylcytosine and 5′-hydroxymethylcytosine by immunolocalisation in the early embryo. Reproduction, Fertility and Development doi: 10.1071/RD14136. 27(5):755-64. doi: 10.1071/RD14136.

O'Neill C, Li Y, Jin XL. (2015) Survival signalling in the preimplantation embryo. Adv Exp Med Biol.;843:129-49. doi: 10.1007/978-1-4939-2480-6_5

Duranthon, V. et al (2015) Chapter 18 Le developpement pre-implantatoire. In ‘La Reproduction animale et humaine’. Eds Saint-Dizier, M. Chastant, S. Editions Quae. RD10, 78026 Versailles Cedex. 978-2-7592-2209-4 1777-4624.

Fenelon, J. C., et al. (2014). Paf-receptor expression in the marsupial embryo and endometrium during embryonic diapause. Reproduction 147(1): 21-31.

Celik, S., et al. (2014). The exit of mouse embryonic fibroblasts from the cell-cycle changes the nature of solvent exposure of the 5´-methylcytosine epitope within chromatin. PLoS ONE 9(4): e92523.

Wong, J. C. Y., et al (2014). The Epigenetic Bivalency of Core Pancreatic β-Cell Transcription Factor Genes within Mouse Pluripotent Embryonic Stem Cells Is Not Affected by Knockdown of the Polycomb Repressive Complex 2, SUZ12. PLoS ONE 9(5): e97820.

Jin XL, O'Neill C. (2014) Systematic analysis of the factors that adversely affect the rate of cell accumulation in mouse embryos during their culture in vitro. Reprod Biol Endocrinol. 12:35.

Bertoldo MJ, et al (2014) Impacts of and interactions between environmental stress and epigenetic programming during early embryo development. Reproduction, Fertility and Development. ;27(8):1125-36. doi: 10.1071/RD14049.


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